Back to Search
Start Over
Wenxin Keli diminishes Ca2+ overload induced by hypoxia/reoxygenation in cardiomyocytes through inhibiting INaL and ICaL
- Source :
- Pacing and Clinical Electrophysiology. 40:1412-1425
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- Background An increase in the late sodium current (INaL ) causes intracellular Na+ overload and subsequently intracellular Ca2+ ([Ca2+ ]i ) overload via the stimulated reverse Na+ -Ca2+ exchange (NCX). Wenxin Keli (WXKL) is an effective antiarrhythmic Chinese herb extract, but the underlying mechanisms are unclear. Methods and results The INaL , NCX current (INCX ), L-type Ca2+ current (ICaL ), and action potentials were recorded using the whole-cell patch-clamp technique in rabbit ventricular myocytes. Myocyte [Ca2+ ]i transients were measured using a dual excitation fluorescence photomultiplier system. WXKL decreased the enhanced INaL , reverse INCX , diastolic [Ca2+ ]i , and the amplitude of Ca2+ transients induced by sea anemone toxin II (ATX II, a specific INaL channel opener) in a concentration-dependent manner. Hypoxia increased INaL , INCX , and diastolic [Ca2+ ]i , and decreased amplitude of [Ca2+ ]i transients. Hypoxia-reoxygenation aggravated these changes and induced spontaneous [Ca2+ ]i transients and hypercontraction in 86% cells (6/7). The application of WXKL during hypoxia or reoxygenation periods decreased the increased INaL , INCX , and diastolic [Ca2+ ]i , and prevented those events in 82% cells (9/11) under hypoxia-reoxygenation conditions. WXKL also inhibited the ICaL in a dose-dependent manner. Furthermore, WXKL shortened the action potential duration and completely abolished ATX II-induced early afterdepolarizations from 9/9 to /9. In isolated heart electrocardiogram recordings, WXKL inhibited ischemia-reperfusion induced ventricular premature beats and tachycardia. Conclusions WXKL attenuated [Ca2+ ]i overload induced by hypoxia-reoxygenation in ventricular myocytes through inhibiting INaL and ICaL and prevents arrhythmias. This could, at least partly, contribute to the antiarrhythmic effects of WXKL.
- Subjects :
- 0301 basic medicine
Tachycardia
business.industry
Diastole
General Medicine
030204 cardiovascular system & hematology
Pharmacology
Hypoxia (medical)
Afterdepolarization
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
medicine
Myocyte
Wenxin keli
medicine.symptom
Cardiology and Cardiovascular Medicine
business
Intracellular
Ca2 overload
Subjects
Details
- ISSN :
- 01478389
- Volume :
- 40
- Database :
- OpenAIRE
- Journal :
- Pacing and Clinical Electrophysiology
- Accession number :
- edsair.doi...........afeea34c0af4c0e391afdae0cb9065ae